The objective of the proposed research is to clarify the pathology of iron metabolism at the cellular level and thereby to help create means for better, more rational therapies of diseases associated with disturbed iron metabolism. We propose to investigate: (1) events whereby normal rat cells in vivo and neoplastic rat cells in vitro dispose of excess iron under various conditions; (2) the role of protein subunits of ferritin in iron-absorbing intestinal mucosal cells in states of iron excess and iron deficiency; (3) the inheritance of two rat heart alloferritins discovered in our laboratory; (4) the possibility that humoral signals are implicated in absorption of iron from the intestine. Several strains of rats as well as hybrid rats bred from the ACI and Sprague-Dawley strains, and a clonally derived line of rat hepatoma cells growing in vitro will be used. Methods include: for (1), (2) and (3), above, radioimmunoassay of biosynthetically (14C, 59Fe)-labeled ferritin protein subunits and of ferritin in cells, cell compartments and cell fractions, as well as immunoelectron microscopic localization; for (3), above, preparation of different cell populations from rat hearts and livers and electrophoresis in several modes to identify isotope-labeled allo- and isoferritins; for (4), above, analyses of absorption from the intestine of 59Fe or 55Fe in the normal or the abnormal partner of pairs of rats joined by carotid-jugular cross circulation (e.g. normal rat to iron-deficient rat) and assays of labeled iron bound by serum transferrin.